The effect of valacyclovir on secondary prevention of congenital cytomegalovirus infection, following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy. An individual patient data meta-analysis.

OBJECTIVE: Recent studies have shown that a dosage of 8 g/d of oral valacyclovir reduces substantially the vertical transmission rate of cytomegalovirus in women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy. This individual patient data meta-analysis aimed to assess the effectiveness and safety of valacyclovir treatment in the secondary prevention of congenital cytomegalovirus infection. DATA SOURCES: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, the US registry of clinical trials (www. CLINICALTRIALS: gov), and gray literature sources were searched from inception to March 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials and quasi-randomized studies administering 8 g/d of oral valacyclovir in pregnant women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy were included. METHODS: All corresponding authors of the eligible studies were contacted. Cochrane's Risk of Bias 2 and Risk Of Bias In Non-randomised Studies - of Interventions tools were used for the risk of bias assessment. The result of amniocentesis was the primary outcome of interest. A 1-stage individual patient data meta-analysis was performed, using a generalized linear mixed model, clustered by the different trials. A subgroup analysis was performed, assessing separately the effect of valacyclovir in the periconceptional period and first trimester of pregnancy. RESULTS: Overall, 3 studies were included in the analysis (n=527 women). Valacyclovir reduced the vertical transmission rate of cytomegalovirus (adjusted odds ratio, 0.34; 95% confidence interval, 0.18-0.61). This reduction was apparent for both periconceptional period (adjusted odds ratio, 0.34; 95% confidence interval, 0.12-0.96) and first-trimester (adjusted odds ratio, 0.35; 95% confidence interval, 0.16-0.76) infections. Moreover, valacyclovir reduced the rate of neonatal infection (adjusted odds ratio, 0.30; 95% confidence interval, 0.19-0.47), in both periconceptional period (adjusted odds ratio, 0.30; 95% confidence interval, 0.14-0.61) and first-trimester (adjusted odds ratio, 0.30; 95% confidence interval, 0.17-0.54) infections. Furthermore, valacyclovir reduced the rate of termination of pregnancy because of cytomegalovirus-associated severe fetal findings (adjusted odds ratio, 0.23; 95% confidence interval, 0.22-0.24). The gestational age at the initiation of treatment has a positive correlation with all outcomes. The overall prevalence of severe side effects was 2.1%. CONCLUSION: A dosage of 8 g/d of oral valacyclovir reduced the vertical transmission rates of cytomegalovirus following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy, with a low incidence of side effects.

Clinical significance of true umbilical cord knot: a propensity score matching study.

OBJECTIVE: True umbilical cord knot (TUCK) is a rare finding that often leads to intensified surveillance and patient anxiety. This study sought to evaluate the incidence, risk factors, and obstetric and neonatal outcomes of TUCK. METHODS: A retrospective cohort study was conducted at a tertiary university medical center in 2007-2019. Patients with singleton pregnancies diagnosed postnatally with TUCK were identified and compared to women without TUCK for obstetric and neonatal outcomes using propensity score matching (PSM). RESULTS: TUCK was diagnosed in 780 of the 96,766 deliveries (0.8%). Women with TUCK were older than those without TUCK (32.57 vs. 31.06 years, P < 0.001) and had higher gravidity (3 vs. 2, P < 001) and a higher rate of prior stillbirth (1.76% vs. 0.43%, P < 0.01). Following covariate adjustment, 732 women with TUCK were compared to 7320 matched controls. TUCK was associated with emergency cesarean delivery due to non-reassuring fetal heart rate (2.54% vs. 4.35%, P = 0.008, OR 1.71, 95%CI 1.14-2.56) and intrapartum meconium-stained amniotic fluid (19.26% vs. 15.41%, P = 0.022, OR 1.31, 95%CI 1.04-1.65). Neonatal outcomes were comparable except for higher rates of 1-min Apgar score < 7 and neonatal seizures in the TUCK group. The stillbirth rate was higher in the TUCK group, but the difference was not statistically significant (1.23% vs 0.62%, P = 0.06, OR 1.96, 95%CI 0.96-4.03). CONCLUSIONS: TUCK has several identifiable risk factors. Pregnant women with TUCK may cautiously be informed of the relatively low risks of major obstetric or perinatal complications. The lower occurrence of stillbirth in the TUCK group warrants further study.

Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities. DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts. RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy. CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.

Decision-to-delivery interval and neonatal outcomes in intrapartum umbilical cord prolapse.

BACKGROUND: Rapid delivery is important in cases of umbilical cord prolapse to prevent hypoxic injury to the fetus/neonate. However, the optimal decision-to-delivery interval remains controversial. OBJECTIVE: The aim of the study was to investigate the association between the decision-to-delivery interval in women with umbilical cord prolapse, stratified by fetal heart rate pattern at diagnosis, and neonatal outcome. STUDY DESIGN: The database of a tertiary medical center was retrospectively searched for all cases of intrapartum cord prolapse between 2008 and 2021. The cohort was divided into three groups according to findings on the fetal heart tracing at diagnosis: 1) bradycardia; 2) decelerations without bradycardia; and 3) reassuring heart rate. The primary outcome measure was fetal acidosis. The correlation between cord blood indices and decision-to-delivery interval was analyzed using Spearman's rank correlation coefficient. RESULTS: Of the total 103,917 deliveries performed during the study period, 130 (0.13%) were complicated by intrapartum umbilical cord prolapse. Division by fetal heart tracing yielded 22 women (16.92%) in group 1, 41 (31.53%) in group 2, and 67 (51.53%) in group 3. The median decision-to-delivery interval was 11.0 min (IQR 9.0-15.0); the interval was more than 20 min in 4 cases. The median cord arterial blood pH was 7.28 (IQR 7.24-7.32); pH was less than 7.2 in 4 neonates. There was no correlation of cord arterial pH with decision-to-delivery interval (Spearman's Ρ = - 0.113; Ρ = 0.368) or with fetal heart rate pattern (Spearman's Ρ = .425; Ρ = .079, Ρ = - .205; Ρ = .336, Ρ = - .324; Ρ = .122 for groups 1-3, respectively). CONCLUSION: Intrapartum umbilical cord prolapse is a relatively rare obstetric emergency with an overall favorable neonatal outcome if managed in a timely manner, regardless of the immediately preceding fetal heart rate. In a clinical setting which includes a high obstetric volume and a rapid, protocol-based, response, there is apparently no significant correlation between decision-to-delivery interval and cord arterial cord pH.

Antenatal Corticosteroids for Small for Gestational Age in Late Preterm Newborns.

BACKGROUND: The administration of antenatal corticosteroids (ACS) is standard practice for management of threatened preterm birth. Its benefit, especially in small for gestational age (SGA) late preterm, is unclear. OBJECTIVES: To evaluate the impact of ACS on perinatal outcome of late preterm SGA neonates. METHODS: We conducted a retrospective cohort study of all women carrying a singleton gestation who had late preterm delivery (34-36 gestational weeks) of SGA neonates at a single tertiary university-affiliated medical center (July 2012-December 2017). Exclusion criteria included termination of pregnancy, intrauterine fetal death, and birth weight ≥ 10th percentile. Outcomes were compared between ACS and non-ACS treatment prior to delivery. Neonatal composite outcome included neonatal intensive care unit (NICU) admission, respiratory distress syndrome, mechanical ventilation, and transient tachypnea. RESULTS: Overall, 228 women met inclusion criteria; 102 (44.7%) received ACS and 126 did not (55.3%). Median birth weight among the non-ACS group was significantly higher (1896.0 vs. 1755.5 grams P < 0.001). Rates of NICU and jaundice requiring phototherapy were higher among the ACS group (53.92% vs. 31.74%, P = 0.01; 12.74% vs. 5.55%, P = 0.05, respectively). Composite neonatal outcome was significantly higher among the ACS group (53.92% vs. 32.53%, odds ratio [OR] 2.42, 95% confidence interval [95%CI] 1.41-4.15, P = 0.01). After adjustment for potential confounders, this association remained significant (OR 2.15, 95%CI 1.23-3.78, P = 0.007). CONCLUSIONS: ACS given during pregnancy did not improve respiratory outcome for SGA late preterm neonates. ACS may be associated with a worse outcome.

Residential greenness and hair cortisol levels during the first trimester of pregnancy.

BACKGROUND AND AIM: Studies have shown that increased maternal cortisol level is associated with child adverse health outcomes. Hair cortisol (HC) is suitable for assessing long-term circulating cortisol concentration. Only two previous studies reported beneficial associations between cortisol and residential greenness during pregnancy and no study focused on the first trimester. Our aim was to evaluate the association between residential greenness and first trimester HC levels among pregnant women in Israel. METHODS: Women were recruited during second and third trimesters. Hair samples were collected from the scalp and retrospective HC levels during the first trimester were quantified for 217 women. HC levels were natural log transformed and outliers were excluded. Based on geocoded birth address, small area sociodemographic status (SES) and mean residential surrounding greenness were calculated using high-resolution satellite-based Normalised Difference Vegetation Index (NDVI) data at 100, 300 and 500-m buffers in a cross-sectional approach. In addition, longitudinal exposure to mean greenness during a week preconception and during the first trimester were calculated. Missing covariates were imputed and linearity of the associations were evaluated. Generalized linear models were used to estimate the crude and adjusted associations controlled for the relevant covariates. RESULTS: After exclusion of outliers, for 211 women, crude and adjusted beneficial associations between exposure to higher mean NDVI and HC levels were observed for all the exposure measures. An increase in 1 interquartile range of greenness (100 m buffer) was associated with a statistically significant lower estimated natural log mean HC level (-0.27 95% CI: -0.44; -0.11). The associations were robust to adjustment for covariates. The findings were consistent for different buffers, for the longitudinal approach, when all observations were included in the analysis and slightly stronger associations were observed for women with addresses geocoded at the home or street level. For most of the exposure measures, stronger associations were observed among those of lower sociodemographic status. CONCLUSION: Our findings that more greenness associated with reduced maternal cortisol levels measured in the hair during the first trimester, could have substantial implications for urban planners and public health professional. If our observations will be replicated, it may present a useful avenue for public-health intervention to promote health through the provision of greenness exposure during early pregnancy, specifically to disadvantage populations.

The association between chronic liver diseases and preeclampsia.

BACKGROUND: Preeclampsia is a multisystem disorder characterized by an abnormal vascular response to placentation associated with increased systemic vascular resistance. As liver involvement is one of the main clinical features of preeclampsia, we sought to determine if there is an association between chronic liver diseases and preeclampsia. METHODS: A retrospective matched case-control analysis was conducted in a tertiary medical center. Three hundred eleven (311) pregnant women with preexisting chronic liver disease (study group), including viral and autoimmune hepatitis, non-alcoholic fatty liver, Wilson disease, and cirrhosis, were match for age, parity, and number of fetuses to 933 healthy pregnant women (control group). The primary outcome measure was the incidence of preeclampsia in each group. Secondary outcome measures were obstetrical and neonatal complications. Confounders found to be significant on univariate analysis were evaluated using logistic regression models, and odds ratios (OR) and confidence intervals (CI) were calculated. RESULTS: Preeclampsia was diagnosed in 28 women (9.0%) in the study group and 33 women (3.54%) in the control group (p < 0.001). On multivariate analysis adjusted for maternal age, parity, previous preeclampsia, chronic hypertension, gestational diabetes mellitus, pregestational diabetes mellitus, antiphospholipid syndrome, and mode of conception, chronic liver disease was found to be an independent risk factor for preeclampsia (aOR 2.631, 95% CI 1.518-4.561). Although there was no difference in the gestational week at delivery between the groups (38.6 ± 2.13 vs. 38.8 ± 2.17 for study and control group, respectively, p = 0.410), the study group had a lower mean neonatal birthweight (3088 ± 551 vs. 3182 ± 566 g, p = 0.011). There were no between-group differences in the other parameters evaluated. CONCLUSION: In our study, preexisting chronic liver disease was associated with a 2.6-fold increased risk of preeclampsia.

Obstetric and perinatal outcomes in parturients with active SARS-CoV-2 infection during labor and delivery: a retrospective cohort study.

BACKGROUND: The COVID-19 pandemic is an ongoing global healthcare crisis that negatively affects pregnant women. Although patients with an acute infection during pregnancy have been widely studied, information regarding labor and delivery while infected is sparse. The aim of the study was to ascertain maternal, obstetrical, and perinatal outcomes of women who gave birth while infected with SARS-CoV-2. METHODS: Patients diagnosed with COVID-19 during pregnancy at a tertiary medical center in 4/20-2/21 were identified by a retrospective database search. Those with an active intrapartum SARS-CoV-2 infection were compared with those who recovered at least 10 days before labor and delivery. RESULTS: Of the 176 women included in the study, 84 had a SARS-CoV-2 infection at the time of delivery and 92 had recovered from the infection. There was no statistically significant between-group difference in mean gestational age at delivery (39 weeks for both, p = 0.71) and overall rate of cesarean delivery (26.2% vs 17.4%, respectively, p = 0.35) or non-elective cesarean delivery (10.71% vs 4.34%, respectively, p = 0.48). In the active-infection group, the rate of severe disease was 2.4%, and of critical disease (with intensive care unit admission, mechanical ventilation, and ECMO), 3.6%, compared to zero for both in the recovered group. No differences were found between the groups in adverse perinatal outcomes. CONCLUSION: Delivery is safe and feasible in women with active SARS-CoV-2 infection. Nevertheless, we found a non-significant trend for more severe disease and for cesarean delivery and urgent cesarean delivery (for COVID-19-related indications) in women with an intrapartum SARS-CoV-2 infection.

Fetal congenital heart disease - mode of delivery and obstetrical complications.

BACKGROUND: The optimal mode of delivery in cases of fetal congenital heart disease (CHD) is not established. The few relevant studies did not address operative vaginal delivery. The aim of this study was to assess the impact of fetal CHD on mode of delivery during a trial of labor, and to secondarily describe some obstetric complications. METHODS: The database of a tertiary medical center was searched for women who gave birth to a singleton, liveborn neonate in 2015-2018. Mode of delivery was compared between women carrying a fetus with known CHD and women with a healthy fetus matched 1:5 for maternal age, parity, body mass index, and gestational age. RESULTS: The cohort included 616 women, 105 in the CHD group and 511 in the control group. The rate of operative vaginal delivery was significantly higher in the CHD group (18.09% vs 9.78%, OR 2.03, 95% CI 1.13-3.63, p = 0.01); the difference remained significant after adjustment for nulliparity and gestational age at delivery (aOR 2.58, 95% CI 1.36-4.9, p < 0.01). There was no difference between the CHD and control group in rate of intrapartum cesarean delivery (9.52% vs 10.76%, respectively, OR 0.97, 95% CI 0.47-1.98, p = 0.93). The most common indication for operative vaginal delivery was non-reassuring fetal heart rate (78.94% vs 64%, respectively). Median birth weight percentile was significantly lower in the CHD group (45th vs 53rd percentile, p = 0.04). CONCLUSIONS: Our findings suggest that operative vaginal delivery, performed mostly because of non-reassuring fetal heart rate, is more common in pregnancies complicated by a prenatal diagnosis of CHD than non-anomalous pregnancies.

Accurate Diagnosis of Adnexal Torsion-Not Only for Expert Sonographers: A Retrospective Cohort Analysis.

OBJECTIVES: The aim of the study was to evaluate the clinical and sonographic parameters associated with a correct or incorrect diagnosis of adnexal torsion made by resident/attending physicians who are not expert sonographers. METHODS: A retrospective study design included women who presented to the Emergency Department (ED) of a tertiary medical center between 2010 and 2019 with acute lower abdominal pain, who were subsequently diagnosed laparoscopically with adnexal torsion. Women who were correctly diagnosed in the ED by an obstetrician-gynecologist who was not an expert sonographer were compared for clinical and sonographic parameters with women who were initially incorrectly diagnosed and underwent a second ultrasound examination by an expert sonographer following admission. RESULTS: Of 118 women with surgically proven adnexal torsion, 76 were correctly diagnosed in the ED and 42 were initially incorrectly diagnosed. The correctly diagnosed group was characterized by a significantly shorter mean time from admission to surgery, higher rate of vomiting, shorter duration of abdominal pain, and higher rate of prior torsion (P < .05). Physicians who made the correct diagnosis utilized more sonographic parameters than those who did not, namely ovarian size, ovarian edema, and Doppler flow. The correctly diagnosed group had a higher rate of bluish-black (ischemic) adnexa at laparoscopy, but a higher rate of recovery following detorsion. CONCLUSIONS: Physicians in the ED should be alerted to the need to address some basic sonographic features when adnexal torsion is suspected. The diagnostic accuracy of adnexal torsion can be improved by utilizing simple sonographic markers, even in the ED setting.

Glucose tolerance test with a single abnormal value in pregnancy and the risk of type-2 diabetes mellitus.

PURPOSE: To evaluate the association between a single abnormal value on a 3-h 100 g oral glucose tolerance test (OGTT) results and future type-2 diabetes mellitus (Type-2 DM). METHODS: Retrospective cohort study of women between 18 and 45 years of age who underwent a 3-h OGTT during pregnancy and delivered in a tertiary medical center between 2007 and 2014. The women  were followed for a median period of 64 months postpartum. According to OGTT values, women were divided into three groups: normoglycemic (normal OGTT), single abnormal OGTT value (SAV) and gestational diabetes mellitus (two or more abnormal OGTT values, GDM). General pre-pregnancy characteristics, cardiovascular risk factors and future diagnosis of Type-2 DM, as the primary outcome, were recorded. RESULTS: During the study period, 5295 women underwent an OGTT and were followed for a median period of 64 months (interquartile range of 32). The cohort was divided as following: 3639 (68.73%) were normoglycemic, 854 (16.13%) had a SAV in the OGTT and 802 (15.15%) were diagnosed with GDM. Compared with normoglycemic controls, women with SAV and GDM tended to be older (32.20, 33.10 and 31.35 years for SAV, GDM and controls, respectively, p < 0.001); with higher rates of pre-pregnancy obesity (18.62%, 20.77% and 13.22% for SAV, GDM and controls, respectively, p < 0.001), pre-pregnancy hyperlipidemia (13.35%, 15.30% and 10.52% for SAV, GDM and controls, respectively, p = 0.021) and pre-pregnancy chronic hypertension (5.50%, 4.43% and 3.18% for SAV, GDM and controls, respectively, p = 0.01). Post-pregnancy Type-2 DM was diagnosed at a higher rate among women with SAV or GDM (2.69% for SAV, 7.39% for GDM and 0.66% for normoglycemic controls, p < 0.001). Using a cox proportional hazard regression, SAV and GDM were significantly and independently associated with a higher rate of future overt type-2 diabetes (adjusted aOR 3.59 for SAV and 11.38 for GDM, p < 0.001). In a sub-analysis of the OGTT values, overall, abnormal fasting glucose had the highest correlation with developing future Type-2 DM (8.95% compared with 6.02% for OGTT_60, 6.03% for OGTT_120 and 7.35% for OGTT_180, p < 0.001). A predictive model, combining multiple risk factors, as pre-pregnancy obesity and hypertension with SAV complicating the index pregnancy showed a risk as high as 3.40% for developing future Type-2 DM. CONCLUSION: SAV is independently associated with a significant higher rate of future Type-2 DM, as early as 5 years following the index pregnancy.

Amniocentesis in twin gestation: the association between gestational age at procedure and complications.

PURPOSE: Third trimester amniocentesis is often performed when indications arise after 24 weeks of gestation-typically to investigate new sonographic findings, and might be related to pre-term birth. Scarcity of data exists concerning the risks of third-trimester amniocentesis in twin pregnancies. METHODS: A retrospective cohort study of all twin gestations that underwent amniocentesis in a tertiary hospital between 2007 and 2016. Outcomes and procedure-related complications were compared between third-trimester (≥ 24 weeks) and mid-trimester amniocentesis (16-23 weeks). Primary outcome was defined as membrane rupture within four weeks of procedure. Logistic regression analysis was utilized to adjust results to potential confounders. RESULTS: Overall, 185 eligible women were included, of them, 28 (15.1%) underwent third-trimester amniocentesis and 157 (84.9%) underwent mid-trimester amniocentesis. Women in the third-trimester amniocentesis group were younger and presented higher frequencies of intra-uterine growth restriction (31.5 vs. 35.3, p < 0.001, and 28% vs. 10% p = 0.015, respectively). The prevalence of membrane rupture within 4 weeks of the procedure was significantly higher in the third-trimester amniocentesis group (31% vs. 1%, p < 0.001). Delivery rates after third-trimester amniocentesis within 1, 2 and 4 weeks of the procedure were 11%, 14.8% and 52%, respectively, versus 0% following mid-trimester amniocentesis (p < 0.001). Gestational age at delivery was similar between the groups (35.7 vs. 36.4 gestational weeks, p = 0.34). In multivariate analysis, gestational age at amniocentesis was found to be an independent risk factor for premature rupture of membranes within 4 weeks of the procedure. CONCLUSION: Third trimester amniocentesis in twin pregnancies is associated with significantly higher rates of procedure-related membrane rupture compared to mid-trimester amniocentesis.

Mobile Self-Operated Home Ultrasound System for Remote Fetal Assessment During Pregnancy.

Background: Mobile medical devices for self-patient use are a rapidly evolving section of telehealth. We examined the INSTINCT® ultrasound system, a portable, self-operated ultrasound device attached to a commercial smartphone for remote fetal assessment. We aimed to evaluate whether it is feasible to use remote fetal assessment during pregnancy. Materials and Methods: This is an observational noninterventional trial. We included women with a singleton fetus at 14 + 0 to 39 + 6 gestational weeks. Each participant received the device for a self-use period of 7-14 days and was instructed to perform one to three scans a day. Participants completed a self-assessment questionnaire to evaluate safety and usability (i.e., user experience and satisfaction). Each scan was evaluated for fetal heart activity, amniotic fluid volume, fetal tone, fetal body, and breathing movements. Results: One hundred women, completing 1,360 self scans, used the device for 8.1 ± 1.5 days, performing an average of 13.6 ± 6.2 scans each. There were no device-related serious adverse events. Success in detection was 95.3% for fetal heart activity, 88.3% for body movements, 69.4% for tone, 92.2% for normal amniotic fluid volume, and 23.8% for breathing movements. Interobserver agreement was 94.4% for fetal heart rate activity, 85.9% for body movements, 69.5% for fetal tone, 86.9% for amniotic fluid volume, and 94.0% for breathing movements. Self-assessed user experience was rated at 4.4/5, whereas device satisfaction was rated at 3.9/5. Conclusion: The INSTINCT ultrasound system is a feasible solution for remote sonographic fetal assessment. Further studies are needed to assess its role and impact in telehealth antenatal care and fetal surveillance.

Association between progesterone treatment and neonatal outcome in preterm births: a retrospective analysis.

This retrospective study was conducted to determine if infants born prematurely despite prophylactic maternal progesterone treatment during pregnancy may still benefit from its adjunct properties and have decreased neonatal complications. 248 women treated with vaginal/intramuscular progesterone during pregnancy and 2519 controls who gave birth to a preterm newborn (24 + 0-36 + 6 gestational weeks) at a tertiary medical centre in 2012-2019. The primary outcome measure was neonatal infectious composite outcome. Secondary outcome measures were other maternal and neonatal complications. Compared to controls, the study group was characterised by lower gestational age at birth (35.0 ± 2.66 vs. 36.0 ± 2.23 weeks, p < .001), lower birth weight (2294 vs. 2485 g, p < .001), higher rates of neonatal infectious composite outcome (27.82 vs. 21.36%, p = 0.024), NICU admission, periventricular leukomalacia, and mechanical ventilation. The higher neonatal infectious composite outcome is likely associated with the lower gestational age at birth in this high-risk group and not the progesterone treatment per se.IMPACT STATEMENTWhat is already known on this subject? Several randomised controlled trials have shown that progesterone administration in pregnancy significantly reduced the rate and complications of preterm birth. A recent study reported that vaginal administration of progesterone during pregnancy was more effective than intramuscular administration in decreasing vaginal group B Streptococcus (GBS) colonisation. This finding raises the question of whether progesterone treatment may have additional benefits besides preventing preterm birth and may reduce neonatal complication rate in preterm infants.What do the results of this study add? This is the first study examining the impact of gestational progesterone exposure on outcomes of preterm infants. The primary objective was a composite measure of infectious neonatal outcomes. Newborns who had progesterone exposure on average had lower gestational age, lower birth weight and higher neonatal infectious composite outcome. The significant difference is explained by lower gestational age.What are the implications of these findings for clinical practice and/or further research? Progesterone is widely used to prevent preterm birth, and may have important additive effects even when prematurity is not avoided. Although the findings did not support our initial hypothesis, they warrant further examination with larger cohorts.

Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Cytomegalovirus is a common congenital infection, with high morbidity after an early primary maternal infection. No effective means exist to prevent viral transmission to the fetus. We aimed to investigate whether valaciclovir can prevent vertical transmission of cytomegalovirus to the fetus in pregnant women with a primary infection acquired early in pregnancy. METHODS: This prospective, randomised, double-blind, placebo-controlled trial was done at the Infectious Feto-Maternal Clinic of Rabin Medical Center (Petach Tikvah, Israel). Pregnant women aged 18 years or older, with serological evidence of a primary cytomegalovirus infection acquired either periconceptionally or during the first trimester of pregnancy, were randomly assigned to oral valaciclovir (8 g per day, twice daily) or placebo from enrolment until amniocentesis at 21 or 22 gestational weeks. Randomisation was done separately for participants infected periconceptionally or during the first trimester and was done in blocks of four. Patients and researchers were masked to participant allocation throughout the entire study period. The primary endpoint was the rate of vertical transmission of cytomegalovirus. Statistical analyses were done according to per-protocol principles. The study was registered at ClinicalTrials.gov, NCT02351102. FINDINGS: Between Nov 15, 2015, and Oct 8, 2018, we enrolled and randomly assigned 100 patients to receive valaciclovir or placebo. Ten patients were excluded, five from each study group; therefore, the final analysis included 45 patients (all singletons) in the valaciclovir group and 45 patients (43 singletons and two sets of twins) in the placebo group. In the valaciclovir group, including both first trimester and periconceptional infections, five (11%) of 45 amniocenteses were positive for cytomegalovirus, compared with 14 (30%) of 47 amniocenteses in the placebo group (p=0·027; odds ratio 0·29, 95% CI 0·09-0·90 for vertical cytomegalovirus transmission). Among participants with a primary cytomegalovirus infection during the first trimester, a positive amniocentesis for cytomegalovirus was significantly less likely in the valaciclovir group (two [11%] of 19 amniocenteses) compared with the placebo group (11 [48%] of 23 amniocenteses; p=0·020. No clinically significant adverse events were reported. INTERPRETATION: Valaciclovir is effective in reducing the rate of fetal cytomegalovirus infection after maternal primary infection acquired early in pregnancy. Early treatment of pregnant women with primary infection might prevent termination of pregnancies or delivery of infants with congenital cytomegalovirus. FUNDING: None.

Prediction of Childhood Obesity from Nationwide Health Records.

OBJECTIVE: To evaluate body mass index (BMI) acceleration patterns in children and to develop a prediction model targeted to identify children at high risk for obesity before the critical time window in which the largest increase in BMI percentile occurs. STUDY DESIGN: We analyzed electronic health records of children from Israel's largest healthcare provider from 2002 to 2018. Data included demographics, anthropometric measurements, medications, diagnoses, and laboratory tests of children and their families. Obesity was defined as BMI ≥95th percentile for age and sex. To identify the time window in which the largest annual increases in BMI z score occurs during early childhood, we first analyzed childhood BMI acceleration patterns among 417 915 adolescents. Next, we devised a model targeted to identify children at high risk before this time window, predicting obesity at 5-6 years of age based on data from the first 2 years of life of 132 262 children. RESULTS: Retrospective BMI analysis revealed that among adolescents with obesity, the greatest acceleration in BMI z score occurred between 2 and 4 years of age. Our model, validated temporally and geographically, accurately predicted obesity at 5-6 years old (area under the receiver operating characteristic curve of 0.803). Discrimination results on subpopulations demonstrated its robustness across the pediatric population. The model's most influential predictors included anthropometric measurements of the child and family. Other impactful predictors included ancestry and pregnancy glucose. CONCLUSIONS: Rapid rise in the prevalence of childhood obesity warrant the development of better prevention strategies. Our model may allow an accurate identification of children at high risk of obesity.

The association between maternal cytomegalovirus urinary excretion and congenital infection rate.

BACKGROUND: In utero Cytomegalovirus (CMV) vertical transmission occurs predominantly during primary maternal infection. There are no known non-invasive methods for diagnosis of fetal infection before delivery, however some risk factors have been suggested. We aimed to evaluate the association between maternal CMV urinary excretion and congenital CMV infection. METHODS: A retrospective cohort study of all women who were diagnosed with primary CMV infection during pregnancy in a single university affiliated tertiary medical center, between 2012 and 2016. We examined congenital CMV infection and disease rates among infants born to women with and without CMV urinary excretion. RESULTS: Overall, 126 women were included, 77 in the positive urinary excretion group, and 49 in the negative urinary excretion group. There was no difference in maternal symptoms between the groups. We found no difference in congenital CMV infection and disease rates between infants born to women with and without urinary excretion of CMV (congenital infection rate 37.1% vs. 24.4%, p = 0.209, congenital disease rate of 18.2% vs. 22.4%, p = 0.648). Women with positive urinary CMV excretion had lower IgG avidity values (36.7% vs 54.6%, p = 0.007), with no additional difference in serology pattern. Compared to asymptomatic women, those with CMV related symptoms did not have significantly higher rates of urinary excretion of CMV (70% vs. 60.5%, p = 0.38) or congenital infection rates (40.7% vs. 31.2%, p = 0.48). CONCLUSION: Among infants of women with primary CMV infection in pregnancy, we did not find an association between urinary excretion of CMV and congenital CMV infection.

Association of term isolated microcephaly with mode of delivery and perinatal outcome - a retrospective case-control analysis.

BACKGROUND: We aimed to evaluate the association of isolated fetal microcephaly measured by ultrasound prior to delivery at term with mode of delivery and perinatal outcome. METHODS: A single-center retrospective study was conducted in 2012-2016. Fetal microcephaly was defined as head circumference > 2 standard deviations of the mean for gestational age and sex. We compared the obstetric, delivery, and outcome parameters of women in whom ultrasound performed up to 10 days prior to term delivery showed isolated fetal microcephaly (study group) or normal head circumference (reference group). Exclusion criteria were intrauterine fetal death, birthweight below the 10th percentile, and antepartum cesarean delivery for any indication. RESULTS: Of 3677 women included in the study, 26 (0.7%) had a late ultrasound finding of isolated fetal microcephaly. Baseline characteristics were similar in the two groups except for estimated fetal weight based on abdominal circumference and biparietal diameter, which was lower in the microcephaly group (3209.8 ± 557.6 vs. 2685.8 ± 420.8 g, p < .001). There was no significant between-group difference in rate of vaginal operative deliveries (11.7% vs 14.8%, respectively, p = 0.372). The study group had no intrapartum cesarean deliveries compared to 6.3% of the reference group (NS). Compared to controls, neonates in the study group were smaller (3323.2 ± 432.2 vs. 2957.0 ± 330.4 g, p < .001), with lower birthweight percentile (60.5 ± 26.5 vs. 33.6 ± 21.5%, p < .001) and were more often males (48.2 vs. 90.0%, p < .001). No significant differences were noted in perinatal outcomes between the groups, including admission to neonatal intensive care unit, intraventricular hemorrhage, 5-min Apgar score < 7, asphyxia, seizures, and sepsis. CONCLUSIONS: Isolated microcephaly in term fetuses is not advantageous for a vaginal delivery, nor does it does not pose a greater than normal risk of adverse perinatal outcome.

The relationship between resited epidural catheters after secondary epidural catheter failure and vaginal delivery: A retrospective case-control study.

BACKGROUND: There are cases where epidural analgesia is initially effective but subsequently fails and needs to be resited. We evaluated the rate of normal vaginal delivery and operative delivery among parturients who had resited epidurals compared to parturients with epidurals that were not resited. METHODS: A retrospective electronic medical review of parturients with a singleton gestation attempting normal vaginal delivery under epidural analgesia between the years 2012-2016 was conducted. Resited epidurals were defined as epidurals that were considered effective but subsequently removed and reinserted. For each resited epidural, two previous and two consecutive deliveries of parturients with normally functioning epidural catheter inserted by the same anesthesiologist were matched controls (non-resited epidurals). RESULTS: There were 35,984 attempted vaginal deliveries with 118 resited epidurals and 472 non-resited epidurals. When adjusted for nulliparity, oxytocin administration, sex and weight of the baby, and maternal BMI, labor epidural catheter replacement was not associated with need for instrumental or caesarean delivery, (OR 1.5, 95% CI 0.91-2.49, P = .11). CONCLUSIONS: Need for labor epidural catheter replacement does not appear to be associated with need for operative delivery based on this single-centre cohort analysis.

Fetal-TAPSE for Surveillance of Cardiac Function in Growth-Restricted Fetuses With a Portosystemic Shunt.

OBJECTIVES: Congenital portosystemic shunt (CPSS) in a growth-restricted fetus may lead to cardiac overload and ultimately hemodynamic imbalance. The aim of the study was to describe the application of tricuspid annular plane systolic excursion (TAPSE) for surveillance of cardiac function in growth-restricted fetuses diagnosed with CPSS. METHODS: The study group consisted of 7 fetuses with growth restriction diagnosed with CPSS between 2018 and 2020. Patients were followed longitudinally every 2 weeks. Sonographic fetal-TAPSE (f-TAPSE) was performed every 2 weeks. At each visit, the following parameters were recorded: estimated fetal weight, biophysical profile, nonstress test, Doppler flow indices, and fetal cardiothoracic index. Postnatal laboratory and imaging tests were retrieved from the medical files. RESULTS: Mean gestational age at diagnosis of CPSS was 32 + 1 weeks. Cardiomegaly was observed in all cases. All portosystemic shunts were classified as intrahepatic. Values of f-TAPSE were above the 95th percentile in 6/7 fetuses at presentation and throughout follow-up. Gestational age at delivery ranged between 36 + 5 and 38 + 5 weeks. Postnatally, spontaneous closure of the shunt was noted in 2 infants. Transient hyperammonemia was diagnosed in 2 neonates, with no signs of the characteristic complication. CONCLUSIONS: In growth-restricted fetuses diagnosed concomitantly with CPSS, f-TAPSE offers a practical sonographic tool for assessment of cardiac function and may serve as an additional clinical marker for follow-up. The appearance of cardiomegaly in growth-restricted fetuses should prompt a dedicated sonographic evaluation of the fetal portal system.